mRNA cytokine profile in peripheral blood cells from chronic hepatitis C virus (HCV)-infected patients: effects of interferon-alpha (IFN-α) treatment

Abstract

SUMMARY Natural immune responses, both cellular and humoral, are not capable of terminating HCV infection in most patients. A role has been suggested for peripheral blood leucocytes (PBL) in viral persistence and clinical implications, as these cells may serve as a viral reservoir and at the same time may be inadequate active participants in antiviral immune reactions. IFN-α administration, although only partially successful, is currently the main therapy available for chronic HCV patients. In addition to its antiviral effects, IFN-α regulates the function of cytokines, their receptors and other molecules of immune importance. The aim of this study was to determine cytokine mRNA expression in PBL derived from chronic HCV patients prior to and at termination of IFN-α treatment. HCV RNA was still observed in sera of most patients (10 out of 14 treated patients) at termination of treatment. In pretreated patients mRNA expression of Th2 (IL-4, IL-6 and IL-10) and Th3 (transforming growth factor-beta (TGF-β)) was observed in only a low percentage of PBL samples from patients, similar to controls. IFN-α treatment led to an elevation in the number of samples expressing these cytokines (significant for IL-4, IL-6, IL-10, tumour necrosis factor-alpha (TNF-α) and TGF-β), accompanied by reduction in liver enzymes but in serum viral load in only ≈ 30% of patients. Expression of TNF-α and TNF-β mRNA was observed in samples from patients but not controls, while no differences were observed for mRNA of classical Th1 cytokines (IL-2 and IFN-γ) between patients before or during treatment as well as controls. The cytokine mRNA profile following IFN-α treatment points to an anti-inflammatory response which does not appear to be involved in termination of the viral infection. The PBL cytokine profile observed in this study may explain the failure of the immune system to eradicate HCV chronic infection and suggests that early treatment in the acute phase of disease with agents that stimulate cytotoxic immune type 1 responses may lead to eradication of HCV infection.